Anti-inflammatory, analgesic, antipyretic and related properties of meloxicam, a new non-steroidal anti-inflammatory agent with favourable gastrointestinal tolerance

Abstract

The anti-inflammatory, analgesic and antipyretic properties of the new non-steroidal anti-inflammatory agent, meloxicam, were investigated in a variety of animal models and compared with the properties of piroxicam, diclofenac, indomethacin and several other NSAIDs. With respect to the total effect of a single oral dose, the anti-exudative effect of meloxicam on carrageenan-induced oedema in the rat exceeded that of all the NSAIDs included in the comparison. Additionally, meloxicam showed the greatest potency of all the compounds examined with respect to adjuvant-induced arthritis in the rat, the granuloma pouch model and the cotton pellet test in the rat. Unlike indomethacin, in the carrageenan pleurisy model in the rat, meloxicam caused both a dose-dependent reduction in exudate volume and also inhibition of leucocyte migration. Meloxicam showed a strong and lasting effect on inflammatory pain in the rat. Like other NSAIDs, but unlike dipyrone, meloxicam had no effect in the hot plate and tail clamp tests, which are used to identify weak central analgesic effects. Unlike dipyrone and like indomethacin, meloxicam had no effect in a model of visceral distention pain. In common with other NSAIDs, meloxicam had no influence on the body temperature of normothermic rats in the anti-inflammatory dose range, but did reduce yeast-induced fever in the rat in a dose-dependent manner. Like piroxicam, meloxicam had a uricosuric effect on rats treated with oxonic acid. Low-dose meloxicam inhibited both bradykinin-induced and PAF-induced bronchospasm in the guinea-pig, but had no effect on acetylcholine-induced bronchospasm. Piroxicam had greater ulcerogenic effects in the rat stomach than meloxicam. The therapeutic range of meloxicam in the rat, with regard to inhibition of adjuvant arthritis, was several times greater than that of piroxicam, indomethacin, diclofenac and naproxen.

Novel Ester and Acid Derivatives of the 1,5-Diarylpyrrole Scaffold as Anti-Inflammatory and Analgesic Agents. Synthesis and in Vitro and in Vivo Biological Evaluation

“…The discrepancy between these results and those found in the cell-based assay could be due to a different inhibitor sensitivity exhibited by the mouse and human COX isozymes, as already reported for other anti-inflammatory compounds. 10 As a matter of the fact, such a dramatic loss in COX inhibitory potency and a drop in selectivity under the HWB assay conditions are common to other selective COX-2 inhibitors, such as valdecoxib, 31,32 etoricoxib, 31,32 lumiracoxib, 33 and rofecoxib, 34,35 as well as tNSAIDs such as nimesulide 16,31 and meloxicam. 36,37 It should be pointed out that, according to the test, 10a, 10c, and 11c exhibited an affinity for COX-2 5-10-fold higher than that for COX-1, which should translate clinically into an acceptable GI safety, and allowing for a sufficient prostacyclin generation that should mitigate the CV effects showed by overly selective COX-2 inhibitors, as previously discussed.…”

“…5,9 In fact, a marked intersubject variability in COX-2 inhibition by NSAIDs, in part due to a genetic background, has been shown. 10,11 Despite the fact that several NSAIDs with suitable pharmacodynamic features are available (e.g., [3][4][5], most of them have short half-life, which leads to their administration at high doses (often overshooting) to extend the pharmacodynamic effects, and in addition, some of them displayed hepatic toxicity (i.e., 5).…”

Avian scavengers and the threat from veterinary pharmaceuticals

“…By contrast, veterinary professionals reported few side effects from meloxicam (table 1), though this might partly be because it had been in use for a short time. Meloxicam is a second generation NSAID with preferential cyclooxygenase-2 (COX-2) inhibition and reduced risk of adverse side effects [35], including gastro-intestinal problems [36], than non-selective COX inhibiting drugs like diclofenac. Advocating the pharmacological and drug safety benefits of properly formulated versions of meloxicam to veterinarians and farmers in the Indian sub-continent may be beneficial for vulture conservation and animal welfare, and hasten the switch from diclofenac to 'vulture-safe' meloxicam [37].…”

Acute physiological responses to castration-related pain in piglets: the effect of two local anesthetics with or without meloxicam

“…Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) with a half-life of 2.7 h in piglets (Fosse et al, 2008), which inhibits prostaglandin synthesis by selective blocking of the enzyme cyclooxygenase-2, conferring to this drug analgesic, antipyretic and anti-inflammatory properties (Engelhardt et al, 1995). It is well known that the use of NSAID such as meloxicam provide prolonged analgesia and relieves stress and pain associated with surgical castration (Keita et al, 2010;Hansson et al, 2011;Kluivers-Poodt et al, 2013).…”